Evening primrose oil

Identification

Name

Evening primrose oil

Accession Number

DB11358

Type

Small Molecule

Groups

Investigational, Nutraceutical

Description

Evening primrose oil comes from the extraction from Oenothera biennis seeds and it is commonly used as an alternative source for omega-6 essential fatty acids. In its composition it presents some fatty acids such as Alpha-Linolenic Acid and Gamolenic acid.[1] Evening primrose oil has been filled for the FDA by Humanetics Corporation on April 2000 to be a new dietary ingredient but its current status is "Inadequate basis for expectation of safety".[5] By Health Canada, evening primrose oil is approved in over-the-counter combination dietary supplements.[6] By the EMA, evening primrose oil is approved in herbal preparations.[7]

Pharmacology

Indication

Evening primrose oil is used as part of over-the-counter dietary supplements.[6]

It is also used for the treatment of systemic inflammatory diseases and for women's health conditions such as cyclical mastalgia. These indications do not have sufficient evidence of their effectiveness. It was used for the treatment of atopic dermatitis in the United Kingdom but it is currently withdrawn due to lack of evidence of effectiveness.[1]

The effectivity of evening primrose oil is debatable as the evidence is very limited.[9] Evening primrose oil improves the essential fatty acid content in plasma, erythrocyte, and platelet lipids. It has also been registered to increase alpha-tocopherol levels in non-diabetic and type I diabetic patients. Evening primrose oil affects the fatty acid composition of serum lipids and adipose tissue as well as it helps maintain normal cellular structures and it serves as a prostaglandin precursor. Administration of evening primrose oil is part of long-term therapy and thus, immediate results are never expected.[4]

Mechanism of action

Evening primrose oil presents a content of 74% Alpha-Linolenic Acid and 9% Gamolenic acid from which the later seems to be the key active ingredient of this oil. These major essential fatty acids are required for the normal structure of cell membranes and they are not synthesized endogenously.[4] The therapeutic activity of evening primrose oil is attributed to the direct action of its essential fatty acids on immune cells as well as to an indirect effect on the synthesis of eicosanoids. The actions of highly unsaturated fatty acids in tissues and eicosanoids are thought to be implicated in inflammatory and immunologic pathogeneses.[1]

The essential fatty acids found in evening primrose oil are involved in the biosynthesis of prostaglandin. For this activity, the main involved component is the Gamolenic acid. The presence of this essential fatty acid allows the synthesis of anti-inflammatory substances such as 15-hydroxy-eicosatrienoic acid and prostaglandin E1.[4]

Absorption

The pharmacokinetics of evening primrose oil is mainly studied by analyzing its active ingredient Gamolenic acid. After administration, Gamolenic acid is rapidly absorbed and converted directly to Dihomo-gamma-linolenic acid and other precursors.[4] When orally administered, the tmax was directly dependent to the time of administration, being of 2.7 hours in the evening and 4.4 hours in the morning. The Cmax and AUC were registered to be approximately 21 mcg/ml and 274 mcg.h/ml.[2] The bioavailability of Gamolenic acid acid is influenced by triglyceride composition, cellular kinetics of phospholipases and acyltransferases.[3]

Volume of distribution

No pharmacokinetic data available.

Protein binding

No pharmacokinetic data available.

Metabolism

The main component of evening primrose oil, Alpha-Linolenic Acid is usually desaturated by delta-6-desaturase which transforms this fatty acid to Gamolenic acid. This metabolic activity usually is limited by external factors such as stress, aging, alcohol, smoking, inflammation, diabetes, etc. In presence of these circumstances, the linoleic acid gets accumulated in the body and it inhibits the activity of the enzyme delta-6-desaturase. In proper conditions, Gamolenic acid forms Dihomo-gamma-linolenic acid by the action of elongases and it can further act as a substrate for production of prostaglandins or to be denaturated to arachidonic acid.[4]

The major components of the primrose oil are highly metabolized and the majority of the generated metabolites are excreted in the urine.[8]

Half life

No pharmacokinetic data available.

Clearance

No pharmacokinetic data available.

Toxicity

Evening primrose oil seems to have little toxicological effect in humans. The reported LD50 values in the mouse are 3.12 x 10^4 mcg/kg. The toxicological effects are very minimal and it has proven to not have an effect on tumor incidence nor to present effects on fertility studies.[9]

Taxonomy

Enzymes

Catalyzes the first and rate-limiting reaction of the four that constitute the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process, allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids/VLCFAs per cycle. Condensing enzyme that acts specifically toward polyunsaturated acyl-CoA with the higher activity toward C18:3(n-6) acyl-CoA. May participate in the production of monounsaturated and of polyunsaturated VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators.